SGNDV-004 is a phase 1b/2 open-label, multicenter study that will enroll subjects with locally advanced or metastatic gastric cancer, gastroesophageal cancer, and locally advanced or metastatic breast cancer (LA/mGC/GEJC and LA/mBC) that express HER2.
The study has a dose escalation phase evaluating disitamab vedotin plus tucatinib followed by a dose optimization phase. The 2 dose levels identified in the dose escalation phase will be assessed in the optimization phase for both safety and efficacy in HER2-low LA/mBC subjects. Once the safety and efficacy profile of disitamab vedotin plus tucatinib has been established and a disitamab vedotin dose with the optimum benefit/risk ratio has been determined the disitamab vedotin plus tucatinib combination therapy will be evaluated in an expansion phase with 2 expansion cohorts in subjects with HER2-low mGC/GEJC and HER2 + LA/mBC.
Arms and Interventions
Dose Escalation Phase
Population and HER2 Status
HER2-expressing (IHC 1+ or higher) 2L LA/mGC/GEJC, or 3L or higher LA/mBC
Open-Label Study Treatment
Combination therapy: Disitamab vedotin (dose may vary) + Tucatinib (fixed dose)
Optimization/Expansion
(Planned/Not enrolling yet)
Population and HER2 Status
TBD
Open-Label Study Treatment
TBD
Inclusion Criteria
This is not a complete list of inclusion and exclusion criteria. Please connect with a Principal Investigator for further information.
General Inclusion criteria
- Measurable disease according to RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
Dose escalation cohort
- Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma or breast carcinoma
- Locally-advanced, unresectable, or metastatic stage
- HER2 status IHC 1+ or higher by most recent local assessment.
- Must have experienced disease progression on or after standard of care therapies or be intolerant of standard of care therapies.
Exclusion Criteria
This is not a complete list of inclusion and exclusion criteria. Please connect with a Principal Investigator for further information.
- Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin or tucatinib
- Prior therapy with ADCs with MMAE payload
- Prior therapy with tucatinib
- Active CNS and/or leptomeningeal metastasis.
- Participants who have received prior systemic anticancer treatment including investigational agents within 4 weeks prior to first dose of study treatment
- History of other invasive malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
- Unable to swallow oral tablets or capsules or any significant GI disease which would preclude the adequate oral absorption of medications
Primary outcomes
- Number of participants with dose limiting toxicities DLTs) in dose escalation phase
- Number of participants with adverse events (AEs)
- Number of participants with laboratory abnormalities
- Number of participants with dose alterations
- Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment
Secondary outcomes
- Duration of response (DOR) per RECIST v1.1 by investigator assessment
- Disease control rate (DCR) per RECIST v1.1 by investigator assessment
- Progression free survival (PFS) per RECIST v1.1 by investigator assessment
- Overall survival (OS)
- Pharmacokinetic (PK) parameter - Maximum concentration (Cmax)
- PK parameter - Area under the concentration-time curve to the time of the last quantifiable concentration (AUClast)
- Incidence of anti-drug antibodies (ADAs) against disitamab vedotin
Protocol Amendment 01, DV-004 HCP Page, 14Aug24